Closed loop optimization of control parameters during cardiac pacing

ABSTRACT

A system and method control a pacing parameter in a closed-loop manner by determining a value of an EGM-based index corresponding an optimal electrical activation condition of a patient&#39;s heart and adjusting a pacing therapy to maintain the EGM-based index value. The closed loop control method performed by the system may establish a relationship between an EGM-based index and multiple settings of a pacing control parameter. Values of the EGM-based index are stored with corresponding setting shifts relative to a previously established optimal setting. A processor of an implantable medical device monitors the EGM-based index during cardiac pacing. Responsive to detecting an EGM-based index value corresponding to a non-optimal setting of the control parameter, the processor determines an adjustment of the control parameter from the stored index values and corresponding setting shifts.

RELATED APPLICATION

This application is a continuation of U.S. patent application Ser. No.13/833,882, filed Mar. 15, 2013 entitled “CLOSED LOOP OPTIMIZATION OFCONTROL PARAMETERS DURING CARDIAC PACING”, now U.S. Pat. No. 9,278,219,issued Mar. 8, 2016, which is herein incorporated by reference in itsentirety.

TECHNICAL FIELD

The disclosure relates generally to optimizing control parameters duringcardiac pacing therapies and more particularly to optimizing pacingtherapy control parameters based on relationships between an indexdetermined from intracardiac electrogram (EGM) signals and ventricularactivation.

BACKGROUND

Cardiac resynchronization therapy (CRT) is a treatment for heart failurepatients in which one or more heart chambers are electrically stimulated(paced) to restore or improve heart chamber synchrony. Improved heartchamber synchrony is expected to improve hemodynamic performance of theheart, such as assessed by ventricular pressure and the rate of changein ventricular pressure or other hemodynamic parameters, therebyalleviating symptoms of heart failure. Achieving a positive clinicalbenefit from CRT is dependent on several therapy control parameters,such as the atrio-ventricular (AV) delay and the inter-ventricular (VV)delay. The AV delay controls the timing of ventricular pacing pulsesrelative to an atrial depolarization, intrinsic or paced. The VV delaycontrols the timing of a pacing pulse in one ventricle relative to apaced or intrinsic sensed event in the other ventricle.

Numerous methods for selecting optimal AV and VV delays for use incontrolling CRT pacing pulses have been proposed. For example,clinicians may select an optimal AV or VV delay using Dopplerechocardiography or other imaging modalities to optimize a hemodynamicvariable. Such clinical techniques are time-consuming, require an experttechnician to perform, and are performed at a discreet time, such as atdevice implantation or during a clinical visit, without ongoingadjustment to the CRT therapy parameters as the need may arise. Othermethods may be based on a hemodynamic sensor signal or a sensor ofmechanical heart function. Such methods may require additional sensorsand therefore add cost to the overall system. A need remains, therefore,for a device and method that enables closed loop optimization of CRTtherapy parameters for restoring ventricular synchrony and alleviatingthe symptoms of heart failure associated with ventricular dyssynchrony.

SUMMARY

In general, the disclosure is directed towards techniques forcontrolling a pacing control parameter during a pacing therapy. Inparticular, a control parameter such as a timing parameter, e.g., an AVdelay or a VV delay, is controlled by an implantable medical deviceprocessor using a relationship established between an index derived froman EGM signal and pacing control parameter settings corresponding to anoptimal electrical activation condition and corresponding to non-optimalelectrical activation conditions. An implantable medical deviceprocessor may be configured to determine a value of the EGM-based indexduring an unknown electrical activation condition of a patient's heartand adjust a pacing therapy to maintain the EGM-based index at a valuepreviously established as corresponding to optimal electrical activationsynchrony.

In some examples, an optimal control parameter setting is established bya processor determining a ventricular dyssynchrony index from surfaceECG electrode signals. Activation times are determined from surface ECGsignals that are acquired from multiple surface electrodes. Aventricular dyssynchrony index is determined from the activation times.An optimal setting of the control parameter is determined based on theECG-based ventricular dyssynchrony index, establishing an optimalelectrical activation condition for which the EGM-based indexcorresponding to the optimal activation condition is determined.

The relationship between an EGM-based index and multiple settings of thecontrol parameter is established by delivering cardiac pacing accordingto each of a plurality of control parameter settings, including apreviously established optimal setting and at least one non-optimalsetting different than the optimal setting. The EGM-based index isdetermined from a EGM signal acquired during each of the settings.Values of the determined index are stored with corresponding parametersetting differences or shifts relative to the optimal setting for eachof the multiple settings. The EGM-based index is monitored duringcardiac pacing. Responsive to detecting an EGM-based index valuecorresponding to a non-optimal setting of the control parameter, anadjustment of the control parameter is determined from the storedrelationship between the EGM-based index and corresponding settingshifts.

In one example, a method includes establishing a relationship between anEGM-based index and a plurality of settings of a pacing controlparameter. Establishing this relationship includes delivering cardiacpacing according to each of a plurality of settings comprising apreviously established optimal setting and at least one non-optimalsetting different than the optimal setting by a setting shift,determining the EGM-based index from an EGM signal acquired for each ofthe plurality of settings, and storing values of the determined indexwith corresponding setting shifts relative to the optimal setting foreach of the plurality of settings. The method further includesmonitoring the EGM-based index during cardiac pacing, and, responsive todetecting an EGM-based index value corresponding to a non-optimalsetting of the control parameter, determining an adjustment of thecontrol parameter from the stored index values and corresponding settingshifts. The control parameter is adjusted by the determined adjustment.

In another example, a system includes a plurality of cardiac electrodes,a cardiac signal generator coupled to the plurality of cardiacelectrodes, a sensing module coupled to the plurality of electrodes, anda processor. The cardiac signal generator delivers cardiac pacingaccording to each of a plurality of settings of a pacing controlparameter, the plurality of settings comprising a previously establishedoptimal setting and at least one non-optimal setting different than theoptimal setting by a setting shift. The sensing module senses an EGMsignal during the cardiac pacing. The processor is configured toestablish a relationship between an EGM-based index and the plurality ofsettings by determining the EGM-based index from the EGM signal acquiredfor each of the plurality of settings and storing values of thedetermined index with corresponding setting shifts of each of theplurality of settings relative to the optimal setting. The processor isfurther configured to monitor the EGM-based index during cardiac pacing;and, responsive to detecting an EGM-based index value corresponding to anon-optimal setting of the control parameter, determine an adjustment ofthe control parameter from the stored index values and correspondingsetting shifts. The processor adjusts the control parameter by thedetermined adjustment

In another example a non-transitory, computer-readable storage mediumincludes instructions that, when executed, cause a processor toestablish a relationship between an EGM-based index and a plurality ofsettings of a pacing control parameter, monitor the EGM-based indexduring cardiac pacing, responsive to detecting an EGM-based index valuecorresponding to a non-optimal setting of the control parameter,determine an adjustment of the control parameter from the stored indexvalues and corresponding setting shifts, and adjust the controlparameter by the determined adjustment.

The details of one or more aspects of the disclosure are set forth inthe accompanying drawings and the description below. Other features,objects, and advantages will be apparent from the description anddrawings, and from the claims.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a schematic diagram of one embodiment of an implantablemedical device (IMD) system in which techniques disclosed herein may beimplemented.

FIG. 2 is a block diagram illustrating one example configuration of theIMD shown in FIG. 1.

FIG. 3 is a flow chart of a method for generating EGM-based index valuesaccording to one embodiment.

FIG. 4 depicts look-up table data that may be generated using the methodshown in FIG. 3 according to one embodiment.

FIG. 5 is a flow chart of a method for controlling CRT controlparameters in a closed-loop manner using an EGM-based index.

FIGS. 6A through 6D are a timing diagrams illustrating closed-loopcontrol of an AV delay based on an EGM-based index.

DETAILED DESCRIPTION

Fundamentally, CRT alters electrical activation of the ventricles,improving spatial synchronization of electrical conduction in heartswith electrical conduction disorders such as left bundle branch block,right bundle branch block or other disorders. Optimal electricalactivation of the heart may therefore be important for CRT efficacy.Optimal electrical activation can depend on a number of factorsincluding the location of the pacing electrodes and pacing timingparameters such as AV delay and VV delay. Techniques disclosed hereinenable an IMD to perform closed loop optimization of electricalactivation of the heart.

FIG. 1 is a schematic diagram of one embodiment of an implantablemedical device (IMD) system 100 in which techniques disclosed herein maybe implemented to provide therapy to heart 112 of patient 114. System100 includes IMD 10 coupled to leads 118, 120, and 122 which carrymultiple electrodes. IMD 10 is configured for bidirectionalcommunication with programmer 170. IMD 10 may be, for example, animplantable pacemaker or implantable cardioverter defibrillator (ICD)that provides electrical signals to heart 112 via electrodes coupled toone or more of leads 118, 120, and 122 for pacing, cardioverting anddefibrillating the heart 112. IMD 10 is capable of delivering pacing inone or more heart chambers, and in the embodiment shown, is configuredfor multi-chamber pacing and sensing in the right atrium (RA) 126, theright ventricle (RV) 128, and the left ventricle (LV) 132 using leads118, 120 and 122.

IMD 10 delivers RV pacing pulses and senses RV intracardiac electrogram(EGM) signals using RV tip electrode 140 and RV ring electrode 142. RVlead 118 is shown to carry a coil electrode 162 which may be used fordelivering high voltage cardioversion or defibrillation shock pulses.IMD 10 senses LV EGM signals and delivers LV pacing pulses using theelectrodes 144 carried by a multipolar coronary sinus lead 120,extending through the RA 126 and into a cardiac vein 130 via thecoronary sinus. In some embodiments, coronary sinus lead 120 may includeelectrodes positioned along the left atrium (LA) 136 for sensing leftatrial (LA) EGM signals and delivering LA pacing pulses.

IMD 10 senses RA EGM signals and delivers RA pacing pulses using RA lead122, carrying tip electrode 148 and ring electrode 150. RA lead 122 isshown to be carrying coil electrode 166 which may be positioned alongthe superior vena cava (SVC) for use in deliveringcardioversion/defibrillation shocks. In other embodiments, RV lead 118carries both the RV coil electrode 162 and the SVC coil electrode 166.IMD 10 may detect tachyarrhythmias of heart 112, such as fibrillation ofventricles 128 and 132, and deliver high voltage cardioversion ordefibrillation therapy to heart 112 in the form of electrical shockpulses. Pacing and sensing of the cardiac chambers is typically achievedusing the pace/sense electrodes 140, 142, 144 148 and 150, however insome embodiments coil electrodes 162 and/or 166 may be used in sensingand/or pacing electrode vectors.

While IMD 10 is shown in a right pectoral implant position in FIG. 1, amore typical implant position, particularly when IMD 10 is embodied asan ICD, is a left pectoral implant position. In other embodiments, IMD10 may be implanted in an abdominal location.

IMD 10 includes internal circuitry for performing the functionsattributed to IMD 10. Housing 160 encloses the internal circuitry. It isrecognized that the housing 160 or portions thereof may be configured asan active electrode 158 for use in cardioversion/defibrillation shockdelivery or used as an indifferent electrode for unipolar pacing orsensing configurations with any electrodes carried by leads 118, 120 and122. IMD 10 includes a connector block 134 having connector bores forreceiving proximal lead connectors of leads 118, 120 and 122. Electricalconnection of electrodes carried by leads 118, 120 and 122 and IMDinternal circuitry is achieved via various connectors and electricalfeedthroughs included in connector block 134.

IMD 10 is configured for delivering CRT by delivering pacing pulses inone or both ventricles 128 and 132 for controlling and improvingventricular synchrony. LV pacing may be delivered using a selectedpacing vector that utilizes at least one electrode 144 on multipolar LVlead 120. RV pacing is delivered using RV tip electrode 140 and ringelectrode 142. CRT may be delivered by pacing in a single ventricularchamber (LV or RV) or both chambers (biventricular pacing) depending onpatient need. The methods described herein are implemented in a dual ormulti-chamber pacemaker or ICD delivering pacing pulses to the rightand/or left ventricles using programmable pacing pulse timing parametersand selected pacing vectors.

In some embodiments, IMD 10 is configured to provide “adaptive CRT”which automatically switches between biventricular pacing and LV-onlypacing in response to changes in the patient's intrinsic AV conduction.When AV conduction is impaired or blocked, or more generally when AVconduction time is slowed, biventricular pacing is delivered. Whennormal AV conduction returns, LV-only pacing is delivered. In this way,RV pacing is delivered only when needed based on the patient's own AVconduction status, which may fluctuate over time.

While a multi-chamber ICD is shown in FIG. 1, it is recognized thattechniques disclosed herein may be implemented in a single chamber, dualchamber or multi-chamber pacemaker, with or without anti-arrhythmiatherapies such as cardioversion and defibrillation shock capabilities.For example, techniques disclosed herein for closed-loop optimization ofa CRT control parameter may be used to optimize the AV delay appliedbetween an atrial event, sensed or paced, and a ventricular pacing pulsedelivered in one ventricle (RV or LV only) or biventricular pacingpulses (RV and LV).

Programmer 170 includes a display 172, a processor 174, a user interface176, and a communication module 178 including wireless telemetrycircuitry for communication with IMD 10. In some examples, programmer170 may be a handheld device or a microprocessor-based home monitor orbedside programming device. A user, such as a physician, technician,nurse or other clinician, may interact with programmer 170 tocommunicate with IMD 10. For example, the user may interact withprogrammer 170 via user interface 176 to retrieve currently programmedoperating parameters, physiological data collected by IMD 10, ordevice-related diagnostic information from IMD 10. A user may alsointeract with programmer 170 to program IMD 10, e.g., select values foroperating parameters of the IMD. A user interacting with programmer 170can initiate a CRT optimization procedure performed by IMD 10automatically or semi-automatically, to establish data for closed-loopoptimization of CRT control parameters. As will be described herein, anEGM-based index value, corresponding to varying states of ventricularactivation synchrony as assessed from surface ECG signals, is determinedfrom an EGM signal sensed using selected cardiac electrodes 140, 142,144, 162, 166 or housing electrode 158. The EGM-based index values aredetermined during CRT as it is delivered using varying parametersettings to establish EGM-based index data corresponding to differingstates of ventricular dyssynchrony. The EGM-based index data is used foroptimizing the control parameter in a closed-loop manner by IMD 10. ThisEGM-based index, derived from the EGM signal, is also referred to hereinas an “EGM-based dyssynchrony index” because its relationship to CRTcontrol parameter settings associated with optimal ventricularelectrical synchrony and with non-optimal ventricular electricalsynchrony is established. Knowledge of a patient-specific optimalelectrical synchrony condition is established using surface ECGelectrode signals, and the EGM-based index is recorded for an optimalCRT parameter setting, such as AV delay, as well as multiple non-optimalsettings.

Programmer 170 includes a communication module 178 to enable wirelesscommunication with IMD 10. Examples of communication techniques used bysystem 100 include low frequency or radiofrequency (RF) telemetry, whichmay be an RF link established via Bluetooth, WiFi, or MICS, for exampleas described in U.S. Pat. No. 5,683,432 (Goedeke, et al). In someexamples, programmer 170 may include a programming head that is placedproximate to the patient's body near the IMD 10 implant site, and inother examples programmer 170 and IMD 10 may be configured tocommunicate using a distance telemetry algorithm and circuitry that doesnot require the use of a programming head and does not require userintervention to maintain a communication link.

It is contemplated that programmer 170 may be coupled to acommunications network via communications module 178 for transferringdata to a remote database or computer to allow remote monitoring andmanagement of patient 114 using the techniques described herein. Remotepatient management systems may be configured to utilize the presentlydisclosed techniques to enable a clinician to review CRT therapyparameters and authorize programming of IMD 10. Reference is made tocommonly-assigned U.S. Pat. No. 6,599,250 (Webb et al.), U.S. Pat. No.6,442,433 (Linberg et al.), U.S. Pat. No. 6,418,346 (Nelson et al.), andU.S. Pat. No. 6,480,745 (Nelson et al.) for general descriptions andexamples of network communication systems for use with implantablemedical devices for remote patient monitoring and device programming,all of which patents are hereby incorporated herein by reference intheir entirety.

System 100 further includes an array of surface electrodes 182, whichmay be carried by a belt or strap 180 adapted to be wrapped around thetorso of patient 114 to position electrodes 182 in the vicinity of heart112. Strap 180 is shown inferior to heart 112 in FIG. 1, but it isunderstood that belt 180 may be positioned in a relatively more superiorposition to surround heart 112 such that electrodes 180 are positionednearer to heart 112. Electrodes 182 are used to acquire surface signalsfrom heart 112 during a CRT optimization session. A CRT controlparameter, such as the AV delay and/or VV delay may be optimized byadjusting the parameter until the surface ECG-based determinations ofventricular activation indicate optimally synchronized ventricularactivation. EGM data is then generated by IMD 10 at the optimizedparameter setting and multiple increments/decrements from the optimaldelay setting to establish EGM-based dyssynchrony index data and itsrelationship to increments or decrements from optimal control parametersettings, specific to the patient. The EGM-based data is used by IMD 10to adjust the control parameter in a closed loop to maintain optimizedventricular activation.

In one example illustrated in FIG. 1, strap 180 is wrapped around thetorso of patient 114 such that the electrodes 182 surround heart 112.Electrodes 182 may be positioned around the circumference of patient114, including the posterior, lateral, and anterior surfaces of thetorso of patient 114. In other examples, electrodes 182 may bepositioned on any one or more of the posterior, lateral, and anteriorsurfaces of the torso. Electrodes 182 may be electrically connected toan ECG processing unit 184 via a wired connection 186. Someconfigurations may use a wireless connection to transmit the signalssensed by electrodes 182 to ECG processing unit 184, e.g., as channelsof data.

Although in the example of FIG. 1, strap 180 is shown carrying surfaceelectrodes 182, in other examples any of a variety of mechanisms, e.g.,tape or adhesives, may be employed to aid in the spacing and placementof electrodes 182. In some examples, strap 180 may include an elasticband, strip of tape, or cloth. In some examples, electrodes 182 may beplaced individually on the torso of patient 114.

Electrodes 182 may surround heart 112 of patient 114 and record theelectrical signals associated with the depolarization and repolarizationof heart 112. Each of electrodes 182 may be used in a unipolarconfiguration to sense the surface potentials that reflect the cardiacsignals. ECG processing unit 184 may also be coupled to a return orindifferent electrode (not shown) which may be used in combination witheach of electrodes 182 for unipolar sensing. In some examples, there maybe 12 to 16 electrodes 182 spatially distributed around the torso ofpatient 114. Other configurations may have more or fewer electrodes 182.

ECG processing unit 184 may record and analyze the surface potentialsignals, referred to generally herein as “ECG” signals, sensed byelectrodes 182. Processing unit 184 may be configured to provide anoutput to a user indicating electrical dyssynchrony of heart 112. Theuser may make a diagnosis, prescribe CRT, position therapy devices,e.g., leads, or adjust or select treatment parameters based on theindicated electrical dyssynchrony.

ECG processing unit 184 may compute activation times directly fromsensed surface potential signals. An activation time for each electrodelocation (of electrodes 182) may be determined as a time period betweentwo events, such as between the QRS complex onset and the minimumderivative during the QRS signal (i.e., the steepest negative slope ofthe sensed potential signal) at the respective electrode. Values of oneor more indices indicative of the temporal and/or spatial distributionof the activation times may be determined as measures or indicators ofelectrical dyssynchrony. These indicators of electrical dyssynchrony maybe used to evaluate different CRT control parameters and identify anoptimal CRT control parameter.

Examples of indices of cardiac electrical dyssynchrony that may becalculated from surface potential signals sensed by electrodes 182include a standard deviation of the determined activation times, a rangeof activation times, and a percentage of late activations. All or asubset of the surface electrodes (e.g., only electrodes located on theleft anterior, left lateral and left posterior regions of the torso) maybe used for calculation or computation of the activation times. Therange of activation times may be computed as the difference between themaximum and the minimum cardiac activation times determined from all ora subset of electrodes 182. The percentage of late activations estimatesthe percentage of electrodes 182 whose associated activation times aregreater than a certain percentile, for example the 70^(th) percentile,of the QRS complex duration or the determined activation times forelectrodes 182. Techniques for determining indices of electricaldyssynchrony based on surface activation times are generally disclosedin commonly-assigned pre-grant U.S. Patent Publication No. 2012/0283587A1 (Ghosh, et al.) hereby incorporated herein by reference in itsentirety. Indices of electrical dyssynchrony derived from externalsurface ECG leads are generally described. CRT optimization based onsuch indices derived from surface ECG leads can be performed at implantor at patient follow-up visits. Techniques disclosed herein, however,enable tuning of pacing timing parameters in an ongoing closed-loopmanner to maintain optimal electrical activation of the ventricles in apatient-specific manner.

One or more indices of ventricular dyssynchrony based on the surfacepotential signals sensed by electrodes 182 is used to identify anoptimal CRT parameter setting, such as an AV or VV delay. A user mayprogram the AV delay into IMD 10 using programmer 170. In someembodiments, ECG processing unit 184 and programmer 170 are in wired orwireless communication or integrated in a common device that enablessystem 100 to automatically step through multiple CRT parametersettings, record and analyze surface potential signals to obtain one ormore ECG-based indices of ventricular dyssynchrony, and identify andprogram an optimal setting for the CRT parameter based on analysis ofventricular electrical activations determined from surface ECG signalsand the synchrony or dyssynchrony thereof.

The strap 180 carrying electrodes 182 is one illustrative embodiment ofan apparatus that is useful in recording surface ECG signals from whichventricular activation times can be determined. Other surface cardiacsignal recording apparatus may be used for acquiring cardiac signal datafrom which ventricular activation times can be computed and used incomputing an index of ventricular dyssynchrony for establishing anoptimal setting of one or more CRT control parameters. Other signalrecording apparatus and techniques may include 12-lead ECG electrodes, avest carrying an array of electrodes, and vectorcardiography.

Once an optimal CRT parameter is established based on optimalsynchronization of electrical activation signals of the ventriclesderived from surface ECG signals, CRT is delivered by IMD 10 using theoptimal parameter setting and multiple non-optimal settings increased ordecreased, i.e. shifted, from the optimal setting. IMD 10 acquires EGMsignals for the optimal setting and multiple non-optimal settings toestablish EGM parameter data for differing states of ventricularactivation, i.e. different states of optimal electrical synchrony andnon-optimal electrical synchrony corresponding to different incrementsand/or decrements from the optimal setting of the control parameters.This EGM parameter data is stored by IMD 10 and used in closed-loop CRTcontrol parameter optimization as will be described herein.

FIG. 2 is a block diagram illustrating one example configuration of IMD10. In the example illustrated by FIG. 2, IMD 10 includes a processorand control unit 80, also referred to herein as “processor” 80, memory82, signal generator 84, sensing module 86, and telemetry module 88. IMD10 further includes cardiac signal analyzer 90.

Memory 82 may include computer-readable instructions that, when executedby processor 80, cause IMD 10 and processor 80 to perform variousfunctions attributed throughout this disclosure to IMD 10, processor 80,and cardiac signal analyzer 90. The computer-readable instructions maybe encoded within memory 82. Memory 82 may comprise non-transitory,computer-readable storage media including any volatile, non-volatile,magnetic, optical, or electrical media, such as a random access memory(RAM), read-only memory (ROM), non-volatile RAM (NVRAM),electrically-erasable programmable ROM (EEPROM), flash memory, or anyother digital media with the sole exception being a transitorypropagating signal.

Processor and control unit 80 may include any one or more of amicroprocessor, a controller, a digital signal processor (DSP), anapplication specific integrated circuit (ASIC), a field-programmablegate array (FPGA), or equivalent discrete or integrated logic circuitry.In some examples, processor 80 may include multiple components, such asany combination of one or more microprocessors, one or more controllers,one or more DSPs, one or more ASICs, or one or more FPGAs, as well asother discrete or integrated logic circuitry. The functions attributedto processor 80 herein may be embodied as software, firmware, hardwareor any combination thereof. In one example, cardiac signal analyzer 90may, at least in part, be stored or encoded as instructions in memory 82that are executed by processor and control unit 80.

Processor and control unit 80 includes a therapy control unit thatcontrols signal generator 84 to deliver electrical stimulation therapy,e.g., cardiac pacing or CRT, to heart 112 according to a selected one ormore therapy programs, which may be stored in memory 82. Signalgenerator 84 is electrically coupled to electrodes 140, 142, 144A-144D(collectively 144), 148, 150, 158, 162, and 166 (all of which are shownin FIG. 1), e.g., via conductors of the respective leads 118, 120, 122,or, in the case of housing electrode 158, via an electrical conductordisposed within housing 160 of IMD 10. Signal generator 84 is configuredto generate and deliver electrical stimulation therapy to heart 112 viaselected combinations of electrodes 140, 142, 144, 148, 150, 158, 162,and 166. Signal generator 84 delivers cardiac pacing pulses according toAV and/or VV delays during CRT. These delays are set based on ananalysis of cardiac signals by analyzer 90 as will be described herein.

Signal generator 84 may include a switch module (not shown) andprocessor and control 80 may use the switch module to select, e.g., viaa data/address bus, which of the available electrodes are used todeliver pacing pulses. Processor 80 controls which of electrodes 140,142, 144A-144D, 148, 150, 158, 162, and 166 is coupled to signalgenerator 84 for delivering stimulus pulses, e.g., via the switchmodule. The switch module may include a switch array, switch matrix,multiplexer, or any other type of switching device suitable toselectively couple a signal to selected electrodes.

Sensing module 86 monitors cardiac electrical signals for sensingcardiac electrical events, e.g. P-waves and R-waves, from selected onesof electrodes 140, 142, 144A-144D, 148, 150, 158, 162, or 166 in orderto monitor electrical activity of heart 112. Sensing module 86 may alsoinclude a switch module to select which of the available electrodes areused to sense the cardiac electrical activity. In some examples,processor 80 selects the electrodes to function as sense electrodes, orthe sensing vector, via the switch module within sensing module 86.

Sensing module 86 includes multiple sensing channels, each of which maybe selectively coupled to respective combinations of electrodes 140,142, 144A-144D, 148, 150, 158, 162, or 166 to detect electrical activityof a particular chamber of heart 112. Each sensing channel may comprisean amplifier that outputs an indication to processor 80 in response tosensing of a cardiac depolarization, in the respective chamber of heart112. In this manner, processor 80 may receive sense event signalscorresponding to the occurrence of R-waves and P-waves in the variouschambers of heart 112, e.g. ventricular sense events and atrial senseevents corresponding to intrinsic depolarization of the respective heartchamber. Sensing module 86 may further include digital signal processingcircuitry for providing processor 80 or cardiac signal analyzer 90 withdigitized EGM signals.

The occurrence of R-waves in the ventricles, e.g. in the RV, may be usedin monitoring intrinsic AV conduction time. In particular, prolongationof the AV conduction time or the detection of AV block based on R-wavesensing during no ventricular pacing (or pacing at an extended AV delaythat allows intrinsic conduction to take place) is used to controladaptive CRT in some embodiments. When AV conduction is impaired, signalgenerator 84 is controlled by processor 80 to deliver biventricularpacing, i.e. pacing pulses are delivered in the RV and the LV using aselected AV delay and a selected VV delay. When AV conduction is intact,signal generator 84 is controlled by processor 80 to deliver LV-onlypacing at a selected AV delay to optimally improve ventricular synchronyaccording to an EGM-based parameter whose relationship to ventricularelectrical activation synchrony has been previously established.

As described herein, the AV delay may be optimized uniquely fordifferent heart rhythm states such as rhythm states involving atrialsensing, atrial pacing, LV-only pacing, or biventricular pacing. Forexample, four distinct atrioventricular rhythm states may beevaluated: 1) atrial-sensed, biventricular paced 2) atrial-paced,biventricular paced 3) atrial-sensed, LV-only paced and 4) atrial-pace,LV-only paced. EGM-based ventricular dyssynchrony data may beestablished for different rhythm states and used to adjust the AV delayaccording to the EGM-based data and the current atrial sensing or pacingrhythm state and/or LV-only or biventricular pacing state.

Memory 82 stores intervals, counters, or other data used by processor 80to control the delivery of pacing pulses by signal generator 84. Suchdata may include intervals and counters used by processor 80 to controlthe delivery of pacing pulses to one or both of the left and rightventricles for CRT. The intervals and/or counters are, in some examples,used by processor 80 to control the timing of delivery of pacing pulsesrelative to an intrinsic or paced event in another chamber. Memory 82stores look-up tables and/or equations established for adjusting CRTcontrol parameters such as AV and VV delays as will be described herein.Equations may be stored in the form of coefficient and intercept valuesdefining a relationship between an EGM-based ventricular dyssynchronyparameter and different settings of a control parameter.

FIG. 3 is a flow chart 300 of a method for generating EGM-basedventricular dyssynchrony data for use in closed-loop adjustments of aCRT control parameter according to one embodiment. At block 302,ventricular dyssynchrony is assessed by analyzing activation timesdetermined at multiple surface electrodes as described above and in theincorporated '587 published application. One or more indices ofventricular dyssynchrony are determined for each CRT parameter settingto be tested. Based on the analysis of activation times determined fromsurface electrodes, an optimal CRT parameter setting is identified atblock 304. For example, a CRT control parameter resulting in a minimizedactivation time range, a minimum activation time standard deviation,and/or a minimized percentage of late activation times may be identifiedas an optimal CRT parameter.

One or more CRT parameters may be evaluated. Parameters that may beevaluated include AV delay and VV delay. Furthermore, each of thesetiming parameters may be evaluated during different rhythm conditions orstates, e.g. during atrial sensing and during atrial pacing (withventricular pacing occurring in one or both ventricles). In oneembodiment, AV delay is set to multiple settings during an atrial pacingrhythm and during an atrial sensing rhythm to identify an optimal AVdelay during atrial sensing (SAV delay) and during atrial pacing (PAVdelay).

Additionally, AV delay may be set to multiple settings during pacing inone ventricle, RV-only and/or LV-only, and during biventricular pacing.During biventricular pacing, multiple settings of VV delay may betested. For example, once an optimal AV delay is identified using anominal VV delay, multiple VV delay settings may be applied to determinethe optimal VV delay according to an ECG-based index of ventriculardyssynchrony.

In some embodiments, multiple pacing vectors may be available. Forexample, as shown in FIG. 1, a multi-polar CS lead may include multipleelectrodes available for pacing the LV. Accordingly, an optimal AV delayresulting in a minimized index of ventricular dyssynchrony based onsurface activation time determinations may be identified for eachavailable pacing vector. When a pacing vector is changed, for exampledue to a change in lead impedance or other condition, the AV or VV delaymay be adjusted to an optimal setting identified for the new pacingvector.

Once an optimal setting is established for a CRT parameter block 304,CRT is delivered at the optimal parameter setting(s) at block 306. AnEGM signal is acquired by sensing module 86 and provided to cardiacsignal analyzer 90. Signal analyzer 90 determines a ventriculardyssynchrony parameter from the EGM signal at block 308.

One or more sensing vectors may be selected from the available cardiacelectrodes to provide EGM signals for determining a parameter of the EGMsignal during different control parameter settings. In one embodiment,an EGM sensing vector selected for computing an EGM-based parameter forassessing a ventricular electrical dyssynchrony state is from an LVcathode electrode 144 to RV coil electrode 162 (shown in FIG. 1). Anindex may be computed as the time interval between two fiducial orreference points of the EGM signal. In one embodiment, the EGM-basedindex is determined as the time interval between a maximum amplitude andthe minimum amplitude of an EGM signal during a monitoring window, e.g.a 200 ms window, immediately following a pacing pulse (or after ablanking interval following the pacing pulse). Alternatively, theventricular dyssynchrony index may be determined as the time intervalfrom a pacing pulse to a maximum amplitude of the EGM signal sensed fromthe selected sensing vector. The index may be an averaged value ofmultiple indices obtained from multiple cardiac cycles.

After recording the EGM-based index for the optimal CRT parametersetting at block 308, the parameter setting is increased or decreased atblock 312 to a non-optimal setting by a known increment/decrement. TheEGM-based index is determined for the new setting by returning to block308. This process of increasing or decreasing the CRT parameter by knownincrements/decrements is repeated until an EGM-based index has beenrecorded for all desired CRT parameter test settings as determined atblock 310.

The EGM-based index is stored for each test setting, along with thedifference between the test (non-optimal) setting and the optimalsetting for the CRT parameter at block 314. In this way, an EGM-basedindex is characterized for a known optimal ventricular activationcondition, i.e. the optimal CRT parameter setting identified in responseto surface ECG analysis, and for multiple non-optimal settings. In otherwords, a relationship is established between the EGM-based index andmultiple parameter settings, including the optimal setting and one ormore non-optimal settings different than, i.e. shifted from, the optimalsetting.

Knowing the value of the EGM-based index during optimized electricalactivation of the ventricles, adjustments to the CRT control parametermay be made to return the EGM-based index toward the value associatedwith electrical activation synchrony in a closed-loop control method.The optimal control parameter setting, such as AV delay, may change withchanges in heart rate, activity or other conditions. This variation inan optimal setting occurs when intrinsic AV conduction timing changes.To maintain optimal ventricular activation under changing conditions,the optimal control parameter setting, like the A-V delay, needs to beadjusted so that the relationship of the timing of a CRT ventricularpacing pulse and the timing of intrinsic ventricular conduction remainsconsistent. However, to determine the intrinsic AV conduction and itschanges directly, ventricular pacing needs to be inhibited temporarily,suspending CRT therapy. Even short disruptions in CRT therapy may beundesirable in some patients. By monitoring the EGM-based index and itschanges during CRT pacing, it is possible to detect a need to adjust atiming control parameter without temporary suspension of CRT therapy.

Adjustments to control parameters, like the A-V delay, may be made basedon the stored patient-specific relationship of the EGM-based index toincrements and decrements of the control parameters. In this way, theEGM-based index can be restored to the value associated with optimalelectrical activation synchrony and maintained at this value regardlessof heart rate, intrinsic conduction changes or other changingconditions.

FIG. 4 depicts a look-up table 400 that may be generated using themethod shown in FIG. 3 according to one embodiment. If AV delay is theCRT parameter being optimized, after setting an optimal AV delay basedon a ventricular dyssynchrony index computed from ECG surface potentialsignals, the IMD 10 may be triggered to establish EGM-based index data,for example by a command received from programmer 170.

The signal generator 84 is controlled to deliver a ventricular pacingpulse to one or both ventricles using the previously established optimalAV delay. In the illustrative example, CRT is delivered during fourdifferent rhythm states 402, including single ventricular pacing (LVonly) and biventricular pacing (LV and RV) during both atrial sensingand atrial pacing. Ventricular pacing pulses may be deliveredsimultaneously to the RV and LV during atrial sensing (SAV-BV) 402 a andduring atrial pacing (PAV-BV) 402 c or at a nominal VV interval. Forestablishing the index data during biventricular pacing, a nominal V-Vdelay, e.g. 0 ms, or other previously established value may be used. AnLV-only pulse is delivered during atrial sensing (SAV-LV) 402 b andduring atrial pacing (PAV-LV) 402 d.

During pacing, the ventricular pacing pulses are delivered at varying AVdelays. The cardiac signal analyzer 90 receives a selected EGM signal,e.g. from an LV electrode 144 to RV coil 162 sensing vector or any otheravailable sensing vector, and determines an index from the EGM signal.In one embodiment the EGM-based index is the time interval between amaximum and minimum amplitude in a 200 ms window following theventricular pacing pulse(s).

The EGM-based index 406 is computed during pacing using the optimal AVdelay for each of the rhythm states and stored in the look-up table 400with an associated 0 ms shift from the optimal AV delay setting. The AVdelay shift 404 is the difference between a non-optimal AV delay and theoptimal A-V delay. The EGM-based index is computed and stored formultiple increments and decrements relative to the optimal AV delay. Foreach AV delay setting, the EGM-based index 406 is stored for eachcorresponding AV delay shift 404 relative to the optimal AV delay. Forexample, the AV delay may be decreased by decrements of 10 ms to obtainEGM-based index values at AV delay shifts of −10, −20, −30, −40 and −50ms relative to the optimal AV delay. The AV delay may be additionallyincreased by increments of 10 ms to obtain EGM-based indexes for each AVdelay shift relative to the optimal AV delay of +10, +20, +30, +40 and+50 ms. The size of the AV delay shifts relative to the optimal AV delayand the number of different settings greater and less than the optimalAV delay may vary based on what the optimal delay is, what the intrinsicAV timing interval is for a particular patient, and what range andresolution of settings are available in the IMD.

The shift or difference between the optimal delay and a non-optimaldelay is stored in the look up table 400 instead of the actual delayvalues since the optimal delay resulting in an optimized EGM-based indexvalue will vary with changing heart rate, intrinsic conduction, or otherfactors. It is the relationship between the EGM-based index and relativeshifts (increments or decrements) of the control parameter setting froman optimal setting that is established by collecting the data shown inlook up table 400.

The EGM-based index 406 may be recorded in the look up table 400 in IMDmemory 82 for each rhythm type 402 for multiple AV delay shifts 404relative to the optimal AV delay. It is contemplated that EGM-basedindexes may be determined for establishing look up table data relatingthe EGM-based index values to other CRT control parameters. For example,using an optimal AV delay setting, EGM-based index values can beobtained during pacing using an optimal VV delay (identified fromsurface ECG signal analysis) and multiple shifts from the optimal VVdelay during atrial pacing and/or atrial sensing.

A look-up table of EGM-based index values for different AV and/or VVdelay shifts may be established for multiple pacing vectors. For exampledifferent LV pacing vectors may be selected when a multipolar coronarysinus lead is used. A look-up table 400 may be stored in memory for eachavailable pacing vector or a preferred subset of available pacingvectors.

FIG. 5 is a flow chart 500 of a method for controlling CRT controlparameters in a closed-loop manner using EGM-based index data. Afterestablishing one or more look up tables in IMD memory 82, processor 80uses the look up table data for controlling signal generator 84 toadjust a CRT parameter in response to determinations of the EGM-basedventricular dyssynchrony index made during CRT delivery. In theillustrative example, the CRT parameter being adjusted is AV delay,however, VV delay could be controlled in a closed loop manner based onlook up table data and EGM-based index determinations made during CRT ina similar manner.

At block 502, CRT is delivered using an optimal parameter setting, e.g.AV delay for the current rhythm state (atrial sensing or pacing andLV-only or biventricular pacing) and currently selected pacing vector.The EGM-based index of ventricular dyssynchrony is monitored during CRTdelivery at block 504. For example, sensing module 86 may providecardiac signal analyzer 90 EGM signal data on every ventricular-pacedcardiac cycle to enable continuous monitoring of the ventriculardyssynchrony index. Alternatively, the EGM-based index may be determinedevery Nth paced beat, at regular time intervals or according to anydesired monitoring schedule. In some embodiments, the EGM-based index isat least determined each time a change in a CRT pacing occurs, includingchanges in atrial rate. For example, if the rhythm changes from a sensedatrial rhythm to a paced atrial rhythm or vice versa, if the rhythmchanges between biventricular pacing and single ventricle pacing, if theheart rate changes, or if a pacing vector changes, the ventricularsynchrony condition or state is monitored by determining an index fromthe EGM signal to determine if an adjustment to the AV delay is needed.

At block 506, the value of the EGM-based index determined during CRTdelivery is looked up in a table 400 for the current rhythm state (e.g.SAV-BV, PAV-LV, SAV-BV, or PAV-BV) and stored for the selected pacingvector. If the index is approximately equal to the optimal value storedfor a 0 ms AV delay shift, the AV delay remains unchanged and monitoringcontinues at block 504. If the EGM-based index has changed from theoptimal value, indicating a change in ventricular dyssynchrony, an AVdelay adjustment is determined at block 508. The AV delay adjustment isdetermined from the look up table 400 by looking up the EGM-based indexvalue in the relevant portion of table 400 for the current rhythm state402 and selected pacing vector. The AV delay adjustment is determined asthe same magnitude but opposite polarity or direction of the AV delayshift associated with the current value of the EGM-based dyssynchronyindex.

For example, in reference to look up table 400 of FIG. 4, if the currentrhythm is SAV-BV 402A, and the EGM-based index is determined as being 34ms, the associated AV delay shift is +30 ms. Since this value of theEGM-based index occurred for an AV delay that was shifted +30 ms fromthe optimal AV delay setting, the AV delay adjustment required toimprove ventricular synchrony is −30 ms. By adjusting the current AVdelay setting by −30 ms, the EGM-based index is expected to return toapproximately 50 ms, corresponding to optimally synchronized electricalactivation of the ventricles.

In some cases, an EGM-based index value 406 may be associated with morethan one AV delay shift 404 for a given rhythm 402. For example, in lookup table 400, the EGM-based dyssynchrony index is 80 ms for an AV delayshift of −40 ms and −50 ms during an SAV-BV rhythm 402 a. In this case,the smaller adjustment may be selected first. For example, the AV delaymay be adjusted by +40 ms in response to a determination of theEGM-based dyssynchrony index being 80 ms. Continued monitoring of theEGM-based dyssynchrony index will result in one or more additionaladjustments of the AV delay if the first adjustment does not restore theEGM-based index to its optimal value, e.g. 50 ms in the illustrativeexample. The AV delay is adjusted at block 510 by the adjustmentdetermined at block 508.

If a change in the EGM-based index is detected at block 512 in responseto the adjusted parameter, CRT delivery may continue using the adjustedcontrol parameter. The EGM-based index continues to be monitored atblock 504 and readjustments to the control parameter are made as needed.

In some cases, the EGM-based index may not change in response tomultiple adjustments to a control parameter. In such cases, intrinsic AVconduction block may be detected. In response to no change in theEGM-based index (block 512) following an adjustment of an AV delay, theprocessor and control 80 may control the signal generator 84 to alterthe pacing therapy, e.g. by switching a pacing mode, because of the lossof intrinsic AV conduction. For example, AV block may be detected asevidenced by an EGM-based index value that remains substantiallyunchanged in response to a threshold number of adjustments to AV delay,e.g. three or more adjustments. If LV-only pacing is being delivered, asdetermined at block 514, the signal generator 84 may be switched to abiventricular pacing mode at block 516. Biventricular pacing may bedelivered at a nominal AV delay setting since the EGM-based index isunresponsive to changes in AV delay. The nominal value of AV delay mayrange from 80 to 200 ms for sensed A-V delay and 120 to 250 ms for pacedAV delay. In another embodiment, the IMD may deliver biventricularpacing at the optimal AV delay that was determined initially. In yetanother embodiment the device may deliver pacing at a nominal AV delaywithout switching pacing mode.

The processor 80 may record and store the corresponding value of theEGM-based index at the onset of biventricular pacing (or nominal AVdelay pacing without switching pacing mode) at block 518. Processor 80continues to monitor the EGM-based index for any changes in the EGMindex value.

If a change in the EGM-based index is detected during subsequentmonitoring at block 520, (indicating a possible return of intrinsic AVconduction), the processor 80 may control the signal generator 84 toswitch back to LV-only pacing at block 522 (if a pacing mode switch tobiventricular pacing had been made previously). The EGM-based index ismonitored again relative to its optimal value at blocks 504 and 506.Control parameter adjustments continue as needed to restore and maintainthe EGM-based index at the established value corresponding to optimalelectrical activation.

Using the disclosed techniques, a value for an EGM-based index thatcorresponds to a known state of optimal ventricular electricalsynchrony, as initially determined by ECG-based surface potentialanalysis, is established for one or more rhythm states and/or one ormore pacing vectors. Values of the index associated with non-optimizedcontrol parameter setting shifts, resulting in various states ofventricular dyssynchrony, are also established. This enables adjustmentsto a control parameter to be determined when deviations occur in thevalue of the EGM-based index from its established value at an optimalcontrol parameter setting. An EGM-based index that deviates from theoptimal value during a given rhythm state can be corrected and restoredby adjusting a CRT timing control parameter based on an establishedrelationship between the EGM-based index and control parameter shifts.This relationship may be stored in the form of a look up table as shownin FIG. 4 or in the form of a best fit equation to the data. Anadjustment to a CRT control parameter is determined in response to achange in the EGM-based index by computing a shift from a best fitequation or looking up the associated shift in a look up table. Thetiming control parameter adjustment is the same magnitude but oppositepolarity of the shift relative to the optimal setting.

FIGS. 6A through 6D are timing diagrams illustrating closed-loop controlof the AV delay based on an EGM-based index. In FIG. 6A, timing diagram600 shows the timing of an intrinsic atrial sense event 602 followed bythe time of an expected intrinsic ventricular sense event 604. Anoptimal AV delay 606 for delivering biventricular pacing pulses 608during atrial sensing (SAV) is identified as 100 ms based on analysis ofactivation times determined from surface ECG signals. This optimal SAVdelay 606 may be established during a resting heart rate. For thisoptimal SAV delay 606, the EGM-based index P is determined to be 50 ms,which may be a time interval determined between a maximum and minimumpeak amplitude of the EGM signal following a pacing pulse. Thisdetermination establishes the expected value of the EGM-based index whenthe ventricular activation is known to be in an optimized state ofsynchrony based on surface ECG activation times.

FIG. 6B shows a timing diagram 610 for one example of a non-optimal SAVdelay 616 applied during the same resting heart rate and biventricularpacing conditions as timing diagram 600. The SAV delay has beenincreased to 140 ms, a shift of +40 ms relative to the optimal SAVdelay. Biventricular pacing pulses 618 are delivered after the shiftedSAV delay 616 following a sense atrial event 612. As can be seen, thebiventricular pacing pulses are delivered just prior to an expected (butunknown) time of an intrinsic ventricular depolarization.

The EGM-based index (P) determined at this shifted SAV delay 616 is 30ms. Thus, in a look up table, an EGM-based index value of 30 ms isstored for an SAV-BV rhythm and delay shift of +40 ms.

FIG. 6C is a timing diagram 620 during an increased heart rate, forexample during exercise. The intrinsic ventricular depolarization 624would occur at a shorter intrinsic AV interval after the atrial senseevent 622. However, the timing of the intrinsic ventriculardepolarization 624 is unknown since the ventricles are being paced bybiventricular pacing pulses 628. Without having to detect a change inheart rate or a change in the intrinsic AV interval, the IMD processor80 can adjust the SAV-BV delay 626 automatically by determining theEGM-based index (P) of ventricular dyssynchrony. For the higher heartrate condition shown in FIG. 7C, the SAV delay of 100 ms, which wasoptimal at a resting heart rate, results in an EGM-based index ofventricular dyssynchrony equal to 30 ms. This change in the EGM-basedindex from the optimal 50 ms to 30 ms indicates non-optimal ventricularelectrical activation.

FIG. 6D is a timing diagram 630 illustrating a closed loop adjustment ofthe SAV delay. The EGM-based index value of 30 ms determined during theSAV-BV rhythm shown in FIG. 6C corresponds to an SAV delay shift of +40ms based on the previously obtained data shown in FIG. 6B and stored inthe form of a look up table in IMD memory 82. For this EGM-based indexvalue, an AV delay adjustment 640 of −40 ms (same magnitude but oppositepolarity of the SAV delay shift in FIG. 6B) is indicated. In order torestore the EGM-based index to its optimal value of 50 ms, or as closeas possible to the optimal value, the SAV delay 636 is adjusted by −40ms, to 60 ms. The EGM-based index may be re-determined to verify that ithas returned to a value of approximately 50 ms. A relative increment ordecrement of the AV delay that is needed to restore an optimal EGM-basedindex value is ascertained from the look up table and can be appliedregardless of the actual AV delay setting at the time of the deviated,non-optimal EGM-based index determination.

The relationship between the EGM-based index and ventricular electricaldyssynchrony as a CRT control parameter changes is established bydetermining the EGM-based index for a known optimal ventricularactivation condition and recording the index for multiple conditionsshifted from the optimal ventricular activation condition. Byestablishing this relationship, determinations of the EGM-based indexduring CRT delivery enable closed loop adjustment of a CRT controlparameter without additional sensors and without interrupting CRTtherapy, for example to determine an intrinsic AV conduction time. Inthis way, CRT control parameters are adjusted to restore the EGM-basedindex to a value known to correspond to an optimal electrical activationstate, i.e. optimal ventricular electrical synchrony.

Thus, various embodiments of an IMD system and method for closed loopadjustment of a CRT control parameter have been described. However, oneof ordinary skill in the art will appreciate that various modificationsmay be made to the described embodiments without departing from thescope of the claims. For example, although specific examples of indicesof ventricular dyssynchrony determined from surface ECG activation timeand from an EGM signal, other indices or determinations of ventriculardyssynchrony may be determined from ECG and EGM signals according thetechniques of this disclosure. Furthermore, although an EGM-based indexhas been described herein, it is recognized that an index may bedetermined from other cardiac signals and corresponding index data maybe determined in the manner described herein for establishing arelationship between the index and an optimal ventricular synchronycondition and multiple non-optimal states. Adjustments to pacing therapycontrol parameters may be made to maintain the index at or near anestablished optimal value. These and other examples are within the scopeof the following claims.

The invention claimed is:
 1. A medical device system for optimizing apacing control parameter, comprising: a plurality of cardiac electrodes;a cardiac signal generator coupled to the electrodes for deliveringcardiac pacing pulses; a sensing module coupled to the cardiacelectrodes for acquiring an EGM signal; and a processor configured todetermine a value of an EGM-based index corresponding to an optimalelectrical activation condition of a patient's heart and adjust a pacingtherapy control parameter to maintain the EGM-based index valuecorresponding to the optimal electrical activation condition duringdelivery of the cardiac pacing pulses.
 2. The system of claim 1,wherein: the cardiac signal generator is configured to deliver cardiacpacing according to each of a plurality of settings of a pacing controlparameter, the plurality of settings comprising a previously establishedoptimal setting and at least one non-optimal setting different than theoptimal setting by a setting shift; the processor further configured to:establish a relationship between an EGM-based index and the plurality ofsettings by determining the EGM-based index from the EGM signal acquiredduring cardiac pacing at each of the plurality of settings and storingvalues of the determined index with corresponding setting shifts of eachof the plurality of settings relative to the optimal setting; monitorthe EGM-based index during cardiac pacing; and responsive to detectingan EGM-based index value corresponding to a non-optimal setting of thecontrol parameter, determine an adjustment of the control parameter fromthe stored index values and corresponding setting shifts, and adjust thecontrol parameter by the determined adjustment.
 3. The system of claim2, further comprising a plurality of surface electrodes adapted to bepositioned on a patient's body and a processor for establishing theoptimal setting by computing an index of ventricular dyssynchrony foreach of a plurality of pacing control parameter settings in response tosurface potential signals sensed from the plurality of surfaceelectrodes.
 4. The system of claim 2, wherein the plurality ofelectrodes comprises a left ventricular electrode and a rightventricular coil electrode and acquiring the EGM signal comprisesselecting a sensing vector comprising the left ventricular electrode andthe right ventricular coil electrode.
 5. The system of claim 2, whereinthe processor is further configured to determine a magnitude andpolarity of a setting shift corresponding to the detected EGM-basedindex corresponding to a non-optimal setting; and determine theadjustment as the magnitude and a polarity opposite to the setting shiftcorresponding to the detected EGM-based index.
 6. The system of claim 2,wherein the optimal pacing control parameter comprises an optimalatrio-ventricular (AV) delay used by the signal generator to deliverycardiac resynchronization therapy.
 7. The system of claim 2, wherein theprocessor is further configured to establish the relationship betweenthe EGM-based index and a plurality of settings of the control parameterfor each of a plurality of different heart rhythm states.
 8. The systemof claim 2, wherein the processor is further configured to establish therelationship between the EGM-based index and a plurality of settings ofthe control parameter for each of a plurality of pacing electrodevectors.
 9. The system of claim 2, further comprising a memory forstoring the relationship as a look-up table of determined EGM-basedindex values and associated setting shifts, the memory accessed by theprocessor for determining the adjustment.
 10. The system of claim 2,wherein the processor is further configured to: detect an unchangedvalue of the EGM-based index in response to adjustment of the controlparameter; and switch a pacing mode in response to the unchanged value.11. The system of claim 1, wherein determining the EGM-based indexcomprises detecting a maximum peak amplitude of the EGM signal followinga pacing pulse.
 12. The system of claim 1, wherein determining theEGM-based index comprises determining a time interval between a maximumpeak amplitude and a minimum peak amplitude of the EGM signal followinga pacing pulse.
 13. A medical device system for optimizing a pacingcontrol parameter, comprising: a plurality of cardiac electrodes; acardiac signal generator coupled to the electrodes for deliveringcardiac pacing pulses; a sensing module coupled to the cardiacelectrodes for acquiring an EGM signal; a processor configured todetermine a value of an EGM-based index corresponding to an optimalelectrical activation condition of a patient's heart and adjust a pacingtherapy control parameter to maintain the EGM-based index valuecorresponding to the optimal electrical activation condition duringdelivery of the cardiac pacing pulses; the cardiac signal generator isconfigured to deliver cardiac pacing according to each of a plurality ofsettings of a pacing control parameter, the plurality of settingscomprising a previously established optimal setting and at least onenon-optimal setting different than the optimal setting by a settingshift; the processor further configured to: establish a relationshipbetween an EGM-based index and the plurality of settings by determiningthe EGM-based index from the EGM signal acquired during cardiac pacingat each of the plurality of settings and storing values of thedetermined index with corresponding setting shifts of each of theplurality of settings relative to the optimal setting; monitor theEGM-based index during cardiac pacing; and responsive to detecting anEGM-based index value corresponding to a non-optimal setting of thecontrol parameter, determine an adjustment of the control parameter fromthe stored index values and corresponding setting shifts, and adjust thecontrol parameter by the determined adjustment.
 14. A medical devicesystem for optimizing a pacing control parameter, comprising: aplurality of cardiac electrodes; a cardiac signal generator coupled tothe electrodes for delivering cardiac pacing pulses; a sensing modulecoupled to the cardiac electrodes for acquiring an EGM signal; and aprocessor configured to determine a value of an EGM-based indexcorresponding to an optimal electrical activation condition of apatient's heart and adjust a pacing therapy control parameter tomaintain the EGM-based index value corresponding to the optimalelectrical activation condition during delivery of the cardiac pacingpulses, wherein determining the EGM-based index comprises determining atime interval between a maximum peak amplitude and a minimum peakamplitude of the EGM signal following a pacing pulse.